Protective Effect of Agmatine Against Cisplatin- Induced Cellular Apoptosis in an Auditory Cell Line.

Abstract

Background: The aims of this study were to evaluate the protective effects of agmatine against cisplatin-induced cellular apoptosis in an audi- tory cell line and to prove the protective mechanism of agmatine.

Methods: The House Ear Institute-Organ of Corti 1 cells were co-treated with agmatine at different concentrations and 15 μM of cisplatin for 48 hours. Cell viability and proliferation were measured. Annexin V-fluorescein isothiocyanate /propidium iodide staining was performed to analyze apoptosis. The levels of intracellular reactive oxygen species were measured using flow cytometry. The expression of BCL2-associated X protein and the enzymatic activity of caspase-3 was measured to examine the pathway of apoptosis induction.

Results: In normal conditions, the maximal protective effect occurred with 10 mM of agmatine. However, in the presence of cisplatin, the maximal protective effect was observed from 8 mM of agmatine. Thus, 8 mM was chosen as the ideal agmatine concentration for the analysis of protective effects against cisplatin-induced cytotoxicity. Agmatine exerted a significant protective effect against 15 μM of cisplatin when applied for 48 hours and reduced the proportion of necrotic and late apoptotic cells. Agmatine did not significantly reduce the cisplatin-induced increase in reactive oxygen species but decreased the expression of BCL2-associated X protein and the activity of caspase-3.

Conclusion: Agmatine protected against cisplatin-induced cellular apoptosis in an auditory cell line. These effects were mediated by the pro- tection of mitochondrial function and inhibition of apoptosis.